RAS-AlphaTAC | KRAS-AlphaTACs: a novel class of biotherapeutics to target KRAS

Summary
The RAS pathway is the most frequently activated signaling node in human cancer. Activating KRAS mutations are found in approximately one in seven human cancers. KRAS signaling is also activated in a significant subset of human cancers that lack KRAS mutations. Targeting KRAS has been a central goal during the past four decades, and the efforts have intensified over the past years, ignited by the approval of the KRAS-G12C inhibitors. A targeted KRAS degradation approach is an attractive solution for blocking KRAS activity, and within the Ub-RASDisease project, we explored the degradability of wild-type and mutant KRAS proteins. In parallel, my group initiated studies to combine the Alphabody technology with the targeted protein degradation approach by designing an AlphaTAC as a novel therapeutic modality. The goal of this project is to generate and pre-clinically validate AlphaTACs targeting KRAS for degradation. This will strengthen the Proof of concept on the AlphaTAC utility in targeted protein degradation and provide support for establishing a proprietary platform in view of the creation of a new spin-off company.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/101123405
Start date: 01-08-2023
End date: 31-01-2025
Total budget - Public funding: - 150 000,00 Euro
Cordis data

Original description

The RAS pathway is the most frequently activated signaling node in human cancer. Activating KRAS mutations are found in approximately one in seven human cancers. KRAS signaling is also activated in a significant subset of human cancers that lack KRAS mutations. Targeting KRAS has been a central goal during the past four decades, and the efforts have intensified over the past years, ignited by the approval of the KRAS-G12C inhibitors. A targeted KRAS degradation approach is an attractive solution for blocking KRAS activity, and within the Ub-RASDisease project, we explored the degradability of wild-type and mutant KRAS proteins. In parallel, my group initiated studies to combine the Alphabody technology with the targeted protein degradation approach by designing an AlphaTAC as a novel therapeutic modality. The goal of this project is to generate and pre-clinically validate AlphaTACs targeting KRAS for degradation. This will strengthen the Proof of concept on the AlphaTAC utility in targeted protein degradation and provide support for establishing a proprietary platform in view of the creation of a new spin-off company.

Status

SIGNED

Call topic

ERC-2023-POC

Update Date

12-03-2024
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Horizon Europe
HORIZON.1 Excellent Science
HORIZON.1.1 European Research Council (ERC)
HORIZON.1.1.0 Cross-cutting call topics
ERC-2023-POC ERC PROOF OF CONCEPT GRANTS
HORIZON.1.1.1 Frontier science
ERC-2023-POC ERC PROOF OF CONCEPT GRANTS